The aetiology of sporadic adult‐onset ataxia

Abstract

The nosology and aetiology of sporadic adult-onset ataxia are poorly understood. The aim of the present study was to answer the following questions: (i) How many sporadic ataxia patients have a genetic cause? (ii) How many sporadic ataxia patients suffer from multiple system atrophy (MSA)? (iii) Is there a specific association between sporadic ataxia and serum anti-glutamic acid decarboxylase (GAD) or antigliadin antibodies? and (iv) What are the clinical features of patients with unexplained sporadic ataxia? The study was performed in 112 patients who met the following inclusion criteria: (i) progressive ataxia; (ii) onset after 20 years; (iii) informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years); and (iv) no established symptomatic cause. Thirty-two patients (29%) met the clinical criteria of possible (7%) or probable (22%) MSA. The Friedreich's ataxia mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2 mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in seven (6%). The disease remained unexplained in 65 patients (58%). We did not detect anti-GAD antibodies in any of our patients. Antigliadin antibodies were present in 14 patients, 10 patients with unexplained ataxia (15%) and 4 patients with an established diagnosis (9%). Patients with unexplained sporadic ataxia had a median disease onset of 56.0 years. Decreased vibration sense (62%), decreased or absent ankle reflexes (40%), increased ankle reflexes (39%), dysphagia (38%) and extensor plantar responses and/or spasticity (34%) were the most frequent extracerebellar symptoms. Compared with MSA, disease progression was significantly slower.

Visual Motion Perception Deficits Due to Cerebellar Lesions Are Paralleled by Specific Changes in Cerebro-Cortical Activity

“…The remaining three patients presented with isolated cerebellar atrophy the underlying cause of which could not be specified despite rigorous clinical workup including screening for genetic, metabolic or inflammatory conditions as well as malignancies. According to clinical guidelines these three patients were classified as sporadic adult-onset ataxia (SAOA) (Abele et al, 2002). Since magnetoencephalography is extremely sensitive to muscle activity we also made sure to only include cerebellar patients who, in addition to being able to maintain stable stationary fixation, showed no signs of tremor.…”

Hereditary ataxias: overview

“…A simplex case is a single occurrence of a disorder in a family, sometimes incorrectly referred to as a "sporadic" case. If no acquired cause of the ataxia is identified, the probability is ~13% that the affected individual has SCA1, SCA2, SCA3, SCA6, SCA8, SCA17, or FRDA, 74 and mutations in rare ataxia genes are even less common. 75 Other possibilities to consider are a de novo mutation in a different autosomal dominant ataxia, decreased penetrance, alternative paternity, or a single occurrence of an autosomal recessive or X-linked disorder in a family such as fragile X-associated tremor/ataxia syndrome.…”

The Neuroimmunology of Gluten Intolerance

“…Using the same AGA assay the prevalence of positive AGA in genetically confirmed ataxias was 14/110 (13%), and in healthy volunteers 149/1200 (12%). A number of studies looking at the prevalence of antigliadin antibodies in ataxias have been published (Hadjivassiliou et al, 1996;Burk et al, 2001;Bushara et al, 2001;Luostarinen et al, 2001;Abele et al, 2002;Abele et al, 2003;Ihara et al, 2006;Anheim et al, 2006) The variations in prevalence may relate to geographical differences in the prevalence of CD, referral bias, variability in the AGA assays used, patient selection (some studies included as idiopathic sporadic ataxia patients with cerebellar variant of multi-system atrophy), small number of patients studied and no controls. The common theme in the majority of these studies is the consistently high prevalence of AGA antibodies in sporadic ataxias when compared to healthy controls.…”